Viral infections are an important cause of morbidity and mortality in hospitalized patients. Viruses have also been identified as the probable cause of a number of malignancies including hepatocellular carcinoma and cervical carcinoma. The purpose of this study is to identify viruses that are associated with diseases whose etiology is unknown. Specimens are obtained from patients with clinical syndromes of uncertain cause and highly sensitive assays such as the polymerase chain reaction are performed to attempt to identify viruses that might be present in the blood, body fluids, or tissues. We studied lymph node biopsies from three unrelated patients with fever, rash, and enlarged lymph nodes in which a diagnosis was uncertain. These patients had a normal immune system. The lymph nodes from each of these patients showed viral inclusions in the T cells, that had not be identified using standard tests for several viruses. Using PCR with primers that can recognize a large number of viruses, we identified human herpesvirus 6 in the lymph nodes of these patients. Subsequent staining of the tissue with antibody to human herpesvirus 6 showed viral proteins in the lymph node. Viruses have developed strategies to counteract host defenses so as to allow viruses to infect cells and result in a latent or persistent infection. Another goal of this project is to identify and determine the function of viral proteins that interact with host cell proteins to influence the course of infection. These proteins may allow us to identify new molecules that are important in the human immune system. Programmed cell death (apoptosis) is an antiviral defense mechanism used by the host to eliminate virus-infected cells. Some viruses, which cause chronic infections, encode proteins that inhibit cell death which may allow cells infected with the viruses to avoid destruction by the host's immune system. We are studying the mechanisms by which viral proteins modulate apoptosis.